We plan to determine the crystallographic structure of the OXA-1 oxacillinase, a troublesome bacterial beta-lactamase which provides clinical resistance to beta-lactam antibiotics (penicillins and cephalosporins). A member of the less-characterized class D family of serine beta-lactamases, OXA-1 is especially active against the penicillins oxacillin and cloxacillin and is now found in 10 percent of E. coli clinical isolates. The architecture of the beta-lactam hydrolysis site in OXA-1 will be compared with that in a class A penicillinase and a class C cephalosporinase to understand the preferential ability of OXA-1 to hydrolyze oxacillin and cloxacillin. Because the oxacillinases are poorly inhibited by currently used agents such as clavulanic acid, a crystallographic structure will aid in the design of more effective inhibitors. OXA-1 crystals which diffract to very high resolution (1.5 A) have been examined.